March 31, 2025 • 22 mins
Dr. Dorthe Pedersen unpacks the paradoxical relationship between childhood body size, breast density, and postmenopausal breast cancer risk among a large cohort of Danish women. Her article, “Associations of early life body size and pubertal timing with breast density and postmenopausal breast cancer risk: A mediation analysis,” can be found in the February 2025 (Vol. 102) issue of Annals of Epidemiology.
Read the full article here:
https://www.sciencedirect.com/science/article/pii/S1047279725000109
Episode Credits:
- Executive Producer: Sabrina Debas
- Technical Producer: Paula Burrows
- Annals of Epidemiology is published by Elsevier.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Patrick Sullivan (00:11):
Hello, you're listening to EPITalk
Paper, a monthly podcast fromthe Annals of Epidemiology.
I'm Patrick Sullivan,Editor-in-Chief of the journal,
and in this series we take youbehind the scenes of some of the
latest epidemiologic researchfeatured in our journal.
Today we're here with Dr.
(00:33):
Dorthe Pedersen to discuss herarticle "Associations of Early
Life Body Size and Pubertytiming with breast density and
postmenopausal breast cancerrisk: A mediation analysis.
You can read the full articleonline in the February 2025
issue of the journal at www.
annalsofepidemiology.
org.
(00:53):
So I'd like to introduce ourguest.
Dr.
Dorthe C.
Pedersen is a researchassociate at the Center for
Clinical Research and Prevention, Copenhagen University Hospital
.
Her research focuses on women'shealth in a life course
perspective, with an emphasis onhow early life factors impact
later reproductive health.
Dr.
(01:14):
Pedersen, thank you so much forjoining us today.
Dorthe Pedersen (01:17):
Thank you for inviting me onto the podcast.
I'm very excited to be here.
Patrick Sullivan (01:21):
So I'd first like to ask you just to explain
a little bit about the purposeof the study.
What question were you tryingto answer with this work?
Dorthe Pedersen (01:29):
Yeah, actually it's because we know from
previous studies that the earlylife body size is associated
with risk of post-menopausalbreast cancer, but we don't know
why.
Also, we know that the breastdensity, that is, the amount of
non-fatty tissue in the breast,is an important marker of later
(01:50):
breast cancer risk.
But it's also associated withearly life body size.
So we wanted to investigatewhether breast density might
mediate some of the observedassociations between body size
and breast cancer risk.
So that was the overall aim ofthe study.
Patrick Sullivan (02:01):
So great.
So, with that research question, just walk us through the study
design and, particularly like,the goal here was one of the
substantive pieces is thismediation analysis.
So what's the study design?
How does the mediation analysisget you to that goal?
And just a little bit about whythis is the right methodology
for this question.
Dorthe Pedersen (02:22):
Oh yeah, so I think I will start out with
that, to do this study, we tookadvantage of a large
population-based cohort ofDanish schoolchildren who
underwent legally mandatedhealth examinations in school
and, because we are in Denmark,we have a personal
identification number so we canlink individuals to various
(02:42):
registers.
o this is what we did andobtained information from breast
cancer screening programs onthe breast density, and also we
linked with the Danish breastcancer database to obtain
information on those women wholater developed breast cancer.
First of all, the overall methodis to see whether the childhood
body size is associated withboth the breast density but also
(03:04):
the breast cancer risk.
So this is part of the paperwhere we examine first the
association with breast densityusing generalized linear models
to obtain risk ratios in orderto try to get results that are
easily interpretable instead oflogistic regression, and then we
examine also association withbreast cancer risk using
survival analysis.
(03:25):
And then for the mediationanalysis, which is really the
interesting part, where youdecompose the associations
between the childhood body sizeand the two factors the mediator
and the outcome into direct andindirect effects.
So we chose to do this with thenational effect model that has
been adapted for survivalanalysis so we could get the
(03:46):
results out on the hazard ratios.
But this method we used alsoallowed us to quantify the
amount of the association thatmight be mediated,
Patrick Sullivan (03:55):
S o I want to comment on a couple things.
One is just this idea that oneof the benefits of having a
healthcare structure like youhave which we might call
healthcare, you know, like thatthere's the consistent
identifier across healthcaresettings and some of the early
life surveys even really givesyou a kind of administrative and
(04:18):
healthcare data to be able todo this.
So I think you know the journalis based in the United States
and so the methods that peoplemight use here often don't have
the same confidence in thelinkages or have to be more
ecological because we don't havethat through line.
(04:39):
So I just want to make a case,and maybe the listeners of the
podcast would be on board withthis.
But you know about all thevalues of providing health care
that you know in a systematicway and in a way that's
coordinated across the countryand with other kinds of
identifiers.
So that's my editorial comment.
But in terms of the methodology,I think it's interesting a
couple of pieces that youbrought out here.
One is that you're really kindof choosing the models and the
(05:01):
form and the outcome for moredirect interpretability, which I
know is really appreciated whenit comes to reporting the
results of the study.
And then just this idea oftesting independently
identifying the relationshipbetween childhood BMI and the
breast density, and the breastdensity and the breast cancer
are the components of this.
(05:21):
Did I sort of get that right,yeah?
So, given that, can youdescribe the main findings?
Dorthe Pedersen (05:29):
Of course.
So in the analysis we includedboth information on birth weight
, initial birth weight that willbe self-reported in our cohort
but we have tested it againstthe National Register, so it's
highly correlated.
And then we also tested thechildhood BMI, childhood height
and then timing of puberty,because all of these have shown
in not only in our cohort butalso other cohorts, that there
(05:52):
are associations with the breastcancer risk.
But in our cohort we only foundassociation between childhood
BMI and height, with both breastdensity and breast cancer risk.
So conducting the mediationanalysis, of course we found
that where there was noassociation there was no
mediation either.
But for the childhood BMI wefound that parts of the
(06:13):
association was actuallymediated by breast density,
whereas the positiveassociations we see with
childhood height and breastcancer risk was in fact not
mediated by breast density.
So that gives us an indicationof that other mechanisms might
be in play for theseassociations, but yeah.
Patrick Sullivan (06:30):
Great.
So what were some of thelimitations or potential sources
of bias in the data that youuse and, conversely, what do you
think some of the strengthswere?
Dorthe Pedersen (06:40):
So let's start with the limitations.
Of course there are alwayslimitations when we do studies.
In this study it was that eventhough we have nearly no
selection bias into the cohortbecause it includes virtually
all Copenhagen schools, ineither public or private schools
then, even though breast cancerscreening is offered free of
charge to all Danish women, notall women choose to participate,
(07:02):
so of course there is someselection in those who
participate in the breast cancerscreening.
And also women have to ofcourse, survive from childhood
to adulthood to be included inour studies.
So I think the main limitationis that we might have some sort
of a healthy population we arelooking at and we cannot
preclude some socio-economicselection into the study at
(07:23):
least.
For the strengths, it is thesize of the study population.
Even though we have around200,000 girls in the cohort, we
ended up with around 33,000 inthe study.
That's also quite a largenumber, I think.
And the strength is also thatwe have the measured weight and
height in childhood.
So this really increasesprecision and reduces risk of
(07:44):
misclassification.
And also when we get to thebreast cancer, this is also in a
nationwide register andreporting is mandatory.
So there's really a low risk ofundetected breast cancer
patients.
So yeah, that's what's thestrengths.
Patrick Sullivan (07:58):
Thank you.
Can you say a little bit abouthow administratively difficult
it is to link up these databases?
Is it really just a humansubjects approval process, or
are there a lot of other stepsand complications involved in
being able to link these greatnational data resources that you
use?
Dorthe Pedersen (08:17):
The cohort of the school children is a cohort
we have located where I work.
So of course we had allpermissions in place to have
this cohort.
And then when we link, we needpermission from our national
agency for conducting research.
But in Denmark when you conductregister-based research you
don't need ethical approval, sothat's rather easy, but still
(08:37):
someone needs to approve thatyou are asking a relevant
question for science and forsociety.
Then for this study we obtainedthe information from the breast
cancer screening program.
That was actually different,because this is information from
patient journals going into thehospital.
So we had to request for awaiver for not contacting the
(08:58):
participants by promising thatwe will not contact them and we
will not look at theirindividual data.
But this is for theregister-based research.
And then we got the waiver andthen could conduct a study.
But I think for time spent oncollecting this data that was at
least six months.
So it's not-e ven though sizedata and all the data is
(09:19):
available, it's still atime-consuming process to have
all the permissions in place andso on.
Patrick Sullivan (09:30):
Yeah, it's interesting because I think it's
a reminder that, even whenthese data systems exist and I
think we would all say it's agood thing that at each step
there's a question about what'sindividually identifiable,
what's not, what's coded, andunder what circumstances and
with what understanding were thedata collected and informs that
.
So thanks for reviewing thatfor us Again, like I'm
interested in the topic, butalso in just the potential of
(09:51):
these national data sources thatare linked, so thanks for
sharing a little bit more aboutthat with us.
So I want to wrap up this partby asking what you think the
implications of your findingsare for breast cancer prevention
.
What new recommendations wouldyou make?
Or sometimes our research justraises new questions that get us
on that path.
So what do you think theimplications are here?
Dorthe Pedersen (10:13):
I think, first of all, I would like to say,
because we find that a higherBMI in childhood is actually
seems to be protective againstbreast cancer risk.
I think it's important toemphasize that we do not
recommend girls to gain weightin order to prevent breast
cancer, because all in allobesity is associated with
multiple other adverse healthoutcomes and also several other
cancer forms.
So let us be clear that we arenot recommending this.
(10:36):
But in addition to this, Ithink our results are first step
.
So I think more studies aredefinitely needed before we can
start talking about how this canfeed into other preventive
initiatives, unfortunately.
But I definitely think that,because our results showed that
some of the associated wasmediated by breast density,
there also appears to be adirect effect of the BMI on the
(10:58):
breast cancer risk itself, whichis also supported by a
mendelian randomization studyconducted in the UK Biobank.
So I think it's reallyimportant to look into these
mechanisms before we can starttalking about preventive efforts
.
But yeah, perhaps it will makeus smarter in the future.
Patrick Sullivan (11:16):
I think that is the goal.
You know, like everything's onestep at a time, yeah, so I want
to turn now to a little bitabout some of the human side of
you know how we do our work, howwe come up with our questions
and our identities as people whodo research.
And maybe, starting just to askwhat motivated you to think
about this potentialrelationship between childhood
(11:37):
body size, pubertal timing,postmenopausal breast cancer?
And so, just from a scientificpoint of view, what informs that
?
But also, how did you choosebreast density as the potential
mediator?
So how do you put all thistogether before you started?
Dorthe Pedersen (11:53):
First of all, I'm lucky to be in a research
group where I can build onothers efforts.
So my primary supervisor, mymentor, had this research
project where we were lookinginto different associations with
childhood body size in relationto breast cancer.
So we also did other studies,but for this particular one we
were definitely motivated by theparadox- obesity paradox in
(12:15):
breast cancer.
That is, that we see that ahigh BMI in adulthood is
associated with a high risk ofbreast cancer, postmenopausal
breast cancer.
But when we look in childhoodwe see that a high BMI in
childhood appears to beprotective against
postmenopausal breast cancer andnormally we think that BMI
tracks from childhood toadulthood.
So this is truly a paradox.
(12:37):
We have also, before this,conducted another study where we
were able to generate BMItrajectories across the life
course in a smaller subsampleand from this we saw signals
that it's also the timing thatmatters for the breast cancer
risk.
So those who gain weight earlyon have a lower risk compared to
those who gain weight later inlife and those who gain weight
(12:58):
early in life don't get as highup as those who gain later in
life, if that makes sense.
But of course this is justsignals, but it motivated us to
look into what could thenexplain the association.
And the research group I wasworking with have previously
conducted a study in a differentsubset using a different
(13:20):
measure of breast density, wherethey also find some indication
of that.
It does play a role and becauseI think it's also biologically
possible that having excessweight around the time where the
breast develops that caninterfere with breast
development.
So that was also, it was alsobecause of the biology we
thought of this.
So yes that was how it was puttogether, and then the mediation
(13:44):
has not fully been examined inthe previous study.
So that really was what wewanted to do in this, also with
being able to try to quantifythe amount mediated, so yeah.
Patrick Sullivan (13:55):
Thank you.
So did anything that you foundin this study sort of point you
in a future direction or raisethe next question for you?
Dorthe Pedersen (14:07):
Yeah, for me personally I would say no, not
really the breast cancer.
I'm mostly an epidemiologistand so for me it's more- I would
like to conduct more mediationanalysis in other parts of my
research.
But I definitely think that Ihope that other researchers will
pick up on these results,especially those more into
(14:27):
mechanisms, and try todisentangle how it is that we
see these associations not onlywith the breast entity but also
the more direct effects.
I think that might be somethingwith the genetics, but yeah, I
don't think we have the fulloverview of how genetics works
yet, but.
Patrick Sullivan (14:43):
And thanks for sharing that and this kind of
behind the paper, just part ofthe discussion-
I think it is really interestingwhat you identify, which is
that there are some folks who,as epidemiologists, have a deep
interest in, develop, have ordevelop these deep interest in
methodology.
That is a source of passion,which is amazing.
(15:04):
And there are other folks whomay start with a topical
interest and say, like I'm goingto pick and choose my
collaborators or what I'm goingto learn about to serve my
interest in, like I'm aninfectious disease
epidemiologist, so that andthat's sort of what what drives
me, and I just think it's such apart of the richness of our
profession that there are peoplewho sort of get on both parts
(15:26):
of that path, you know, and thencan bring those skills to other
research questions.
So great to see this as likesomething that sparks an
interest and a passion and thatyou're going to carry forward.
I'm always interested in howpeople get to what they do and
you've said a little bit aboutthis.
But I wonder who, or maybe whatyou think has been the biggest
(15:47):
influence in your career thatsort of led you to what you do
now and to asking these kinds ofquestions.
What put you on this path?
Dorthe Pedersen (15:55):
Yeah, that's a tough question, I think, because
it would be very difficult forme to pinpoint one person or one
thing.
I think a lot of things haveinfluenced my career and also,
you know, choosing to become aresearcher, like my parents,
reading books, and also I'vebeen very fortunate to have
great mentors around me who havegot a dedicated time to guide
me.
But I think for my interest inwomen's health, that actually
(16:19):
traced back to once I wastraveling in Tanzania where I
met some local women and youknow I had a conversation with
them and in less than 10 minutesthey had really taught me about
what privilege is and howeasily you can be blinded by
this, because they had a verydifferent view of women's health
and women's rights than I camewith.
(16:40):
So I think that really put on aspark.
Patrick Sullivan (16:43):
Yeah, that was a spark for your research.
Yeah, so what do you think aresome misconceptions about doing
research or being a researcher?
Dorthe Pedersen (16:54):
That's a great question.
I think two things come to mymind, and one is that people
often think that you have to bebright or very talented to
become a researcher.
But in other sectors I think itrequires that you are curious
and very persistent and you havea willingness to learn from
those around you.
And the other thing is that Ioften hear so you're doing
(17:16):
research.
It's all about new things,testing new hypotheses, getting
new ideas, but actually doingresearch is a very iterative
process, I think, so you keeprepeating the same steps over
and over again to refine yourhypothesis and or approach right
.
So I think people will besurprised that we do a lot of
repetitive work actually inresearch.
Patrick Sullivan (17:38):
Yeah, I think this idea about developing
hypotheses is interestingbecause it speaks to the
different pieces of our sort ofprofessional identities that are
needed to do impactful scienceright, because you do need the
mathematical, the ability towork on that code until it runs,
to interpret the coefficients,to experimentiate things or like
(18:00):
whatever.
You know how are we getting tothe estimates?
But this idea of iterating ideasand our social scientific
networks, that are the soundingboards for us to say, you know,
to articulate ideas orarticulate questions, and what
an amazing professional resourceit is.
When you find yourself in aplace that you can put out a
(18:22):
question and I know for myself,like I always have, there's some
my mind runs a little bit andsays like I don't want to ask
this if somebody has alreadyanswered it and I'm not sure
I've thought through, like ifyou could even get that data,
and so it can be this kind ofself-censoring around our own
feelings of vulnerability orlike recognizing what we don't
know.
But that is the richness ofbeing in a research group, that
(18:45):
is a richness of being, you know, with colleagues, where you
develop that level of comfort,where you can really iterate
together and I think about howmany times like I've come up
with an idea that I thought wasgood and then threw it out, and
maybe then I decided it wasn'tso good, but by the time the
discussion was over, like weended up in a place that was far
better than what I would havecome up with, and so that sort
(19:07):
of scientific village, you know.
Dorthe Pedersen (19:10):
Yeah, I know that process.
It's a hard one but it'srewarding when you get to the,
when you actually get an ideayou think is much better than
the initial one.
Patrick Sullivan (19:20):
Yeah, and then you know related but maybe a
little bit different what advicewould you have for people who
are thinking about being aresearcher either, in terms of
how to prepare, how to decidethings you wish you'd thought
about early on?
Dorthe Pedersen (19:34):
Ah, I think my overall is just to go for it,
actually.
I think, although it's hardwork at times, it's also very
rewarding, as we just talkedabout, when you finally get that
idea that is perhaps new orperhaps helps you crack
something, a problem, orsomething that's fulfilling.
Patrick Sullivan (19:53):
Sometimes we call that the aha moment, like
after thinking and thinking andturning the gears, a little
moment of like aha, like that'sthere actually is a way to do
that.
Yeah, exactly, I find that Iget that more often like hanging
out with colleagues than inmoments of solitude.
But I think different people dodifferent ways.
I definitely know people whoretreat and come back out three
(20:15):
days later with everythingmapped out and I sort of work
well in a social scientificsetting where we brainstorm and
all different ways to do it forsure.
Dorthe Pedersen (20:25):
Yeah, but I think for me it's both.
I think I need some solitudesometimes to really process all
the information, and then, ofcourse, I need to test it with
someone else.
I think learning is somethingyou do in collaboration with
others.
I think it's difficult to do byyourself.
So, yeah, at some point it doesrequire some input.
But also for advice for perhapspeople wanting to pursue a
(20:48):
research career.
I also just want to say thatthey should remember that doing
research is a team effort, as wejust discussed, so they should
always act with this in mind, bekind to people and share credit
and stuff like this, and try tofind a supervisor or mentor
who's also on board with theresearch as a team effort and
(21:08):
not, yeah, just wanted to belonely genius.
Patrick Sullivan (21:14):
That sounds like an amazing place to wrap
this up.
Just the role role of beingkind, seeking mentorship, being
humble, takes us so much fartherthan other ways to get at these
problems.
So thank you, thank you for allthat you shared with us and for
that great sort of thought inwrapping up that brings us to
(21:35):
the end of this episode.
Thank you again, Dr.
Pedersen, for joining us today.
It's been such a pleasure tohave you on the podcast.
Dorthe Pedersen (21:42):
Thank you for inviting me on the podcast.
It was a pleasure toparticipate and I like the
discussion or the greatthoughtful questions.
Patrick Sullivan (21:52):
I'm your host, Patrick Sullivan.
Thanks for tuning in to thisepisode and see you next time on
EPITalk.
Brought to you by Annals ofEpidemiology, the official
journal of the American Collegeof Epidemiology.
For a transcript of thispodcast or to read the article
featured on this episode andmore from the journal, you can
visit us online at www.
(22:13):
annalsofepidemiology.
org.
Hello, you're listening to EPITalk
Paper, a monthly podcast fromthe Annals of Epidemiology.
I'm Patrick Sullivan,Editor-in-Chief of the journal,
and in this series we take youbehind the scenes of some of the
latest epidemiologic researchfeatured in our journal.
Today we're here with Dr.
(00:33):
Dorthe Pedersen to discuss herarticle "Associations of Early
Life Body Size and Pubertytiming with breast density and
postmenopausal breast cancerrisk: A mediation analysis.
You can read the full articleonline in the February 2025
issue of the journal at www.
annalsofepidemiology.
org.
(00:53):
So I'd like to introduce ourguest.
Dr.
Dorthe C.
Pedersen is a researchassociate at the Center for
Clinical Research and Prevention, Copenhagen University Hospital
.
Her research focuses on women'shealth in a life course
perspective, with an emphasis onhow early life factors impact
later reproductive health.
Dr.
(01:14):
Pedersen, thank you so much forjoining us today.
Dorthe Pedersen (01:17):
Thank you for inviting me onto the podcast.
I'm very excited to be here.
Patrick Sullivan (01:21):
So I'd first like to ask you just to explain
a little bit about the purposeof the study.
What question were you tryingto answer with this work?
Dorthe Pedersen (01:29):
Yeah, actually it's because we know from
previous studies that the earlylife body size is associated
with risk of post-menopausalbreast cancer, but we don't know
why.
Also, we know that the breastdensity, that is, the amount of
non-fatty tissue in the breast,is an important marker of later
(01:50):
breast cancer risk.
But it's also associated withearly life body size.
So we wanted to investigatewhether breast density might
mediate some of the observedassociations between body size
and breast cancer risk.
So that was the overall aim ofthe study.
Patrick Sullivan (02:01):
So great.
So, with that research question, just walk us through the study
design and, particularly like,the goal here was one of the
substantive pieces is thismediation analysis.
So what's the study design?
How does the mediation analysisget you to that goal?
And just a little bit about whythis is the right methodology
for this question.
Dorthe Pedersen (02:22):
Oh yeah, so I think I will start out with
that, to do this study, we tookadvantage of a large
population-based cohort ofDanish schoolchildren who
underwent legally mandatedhealth examinations in school
and, because we are in Denmark,we have a personal
identification number so we canlink individuals to various
(02:42):
registers.
o this is what we did andobtained information from breast
cancer screening programs onthe breast density, and also we
linked with the Danish breastcancer database to obtain
information on those women wholater developed breast cancer.
First of all, the overall methodis to see whether the childhood
body size is associated withboth the breast density but also
(03:04):
the breast cancer risk.
So this is part of the paperwhere we examine first the
association with breast densityusing generalized linear models
to obtain risk ratios in orderto try to get results that are
easily interpretable instead oflogistic regression, and then we
examine also association withbreast cancer risk using
survival analysis.
(03:25):
And then for the mediationanalysis, which is really the
interesting part, where youdecompose the associations
between the childhood body sizeand the two factors the mediator
and the outcome into direct andindirect effects.
So we chose to do this with thenational effect model that has
been adapted for survivalanalysis so we could get the
(03:46):
results out on the hazard ratios.
But this method we used alsoallowed us to quantify the
amount of the association thatmight be mediated,
Patrick Sullivan (03:55):
S o I want to comment on a couple things.
One is just this idea that oneof the benefits of having a
healthcare structure like youhave which we might call
healthcare, you know, like thatthere's the consistent
identifier across healthcaresettings and some of the early
life surveys even really givesyou a kind of administrative and
(04:18):
healthcare data to be able todo this.
So I think you know the journalis based in the United States
and so the methods that peoplemight use here often don't have
the same confidence in thelinkages or have to be more
ecological because we don't havethat through line.
(04:39):
So I just want to make a case,and maybe the listeners of the
podcast would be on board withthis.
But you know about all thevalues of providing health care
that you know in a systematicway and in a way that's
coordinated across the countryand with other kinds of
identifiers.
So that's my editorial comment.
But in terms of the methodology,I think it's interesting a
couple of pieces that youbrought out here.
One is that you're really kindof choosing the models and the
(05:01):
form and the outcome for moredirect interpretability, which I
know is really appreciated whenit comes to reporting the
results of the study.
And then just this idea oftesting independently
identifying the relationshipbetween childhood BMI and the
breast density, and the breastdensity and the breast cancer
are the components of this.
(05:21):
Did I sort of get that right,yeah?
So, given that, can youdescribe the main findings?
Dorthe Pedersen (05:29):
Of course.
So in the analysis we includedboth information on birth weight
, initial birth weight that willbe self-reported in our cohort
but we have tested it againstthe National Register, so it's
highly correlated.
And then we also tested thechildhood BMI, childhood height
and then timing of puberty,because all of these have shown
in not only in our cohort butalso other cohorts, that there
(05:52):
are associations with the breastcancer risk.
But in our cohort we only foundassociation between childhood
BMI and height, with both breastdensity and breast cancer risk.
So conducting the mediationanalysis, of course we found
that where there was noassociation there was no
mediation either.
But for the childhood BMI wefound that parts of the
(06:13):
association was actuallymediated by breast density,
whereas the positiveassociations we see with
childhood height and breastcancer risk was in fact not
mediated by breast density.
So that gives us an indicationof that other mechanisms might
be in play for theseassociations, but yeah.
Patrick Sullivan (06:30):
Great.
So what were some of thelimitations or potential sources
of bias in the data that youuse and, conversely, what do you
think some of the strengthswere?
Dorthe Pedersen (06:40):
So let's start with the limitations.
Of course there are alwayslimitations when we do studies.
In this study it was that eventhough we have nearly no
selection bias into the cohortbecause it includes virtually
all Copenhagen schools, ineither public or private schools
then, even though breast cancerscreening is offered free of
charge to all Danish women, notall women choose to participate,
(07:02):
so of course there is someselection in those who
participate in the breast cancerscreening.
And also women have to ofcourse, survive from childhood
to adulthood to be included inour studies.
So I think the main limitationis that we might have some sort
of a healthy population we arelooking at and we cannot
preclude some socio-economicselection into the study at
(07:23):
least.
For the strengths, it is thesize of the study population.
Even though we have around200,000 girls in the cohort, we
ended up with around 33,000 inthe study.
That's also quite a largenumber, I think.
And the strength is also thatwe have the measured weight and
height in childhood.
So this really increasesprecision and reduces risk of
(07:44):
misclassification.
And also when we get to thebreast cancer, this is also in a
nationwide register andreporting is mandatory.
So there's really a low risk ofundetected breast cancer
patients.
So yeah, that's what's thestrengths.
Patrick Sullivan (07:58):
Thank you.
Can you say a little bit abouthow administratively difficult
it is to link up these databases?
Is it really just a humansubjects approval process, or
are there a lot of other stepsand complications involved in
being able to link these greatnational data resources that you
use?
Dorthe Pedersen (08:17):
The cohort of the school children is a cohort
we have located where I work.
So of course we had allpermissions in place to have
this cohort.
And then when we link, we needpermission from our national
agency for conducting research.
But in Denmark when you conductregister-based research you
don't need ethical approval, sothat's rather easy, but still
(08:37):
someone needs to approve thatyou are asking a relevant
question for science and forsociety.
Then for this study we obtainedthe information from the breast
cancer screening program.
That was actually different,because this is information from
patient journals going into thehospital.
So we had to request for awaiver for not contacting the
(08:58):
participants by promising thatwe will not contact them and we
will not look at theirindividual data.
But this is for theregister-based research.
And then we got the waiver andthen could conduct a study.
But I think for time spent oncollecting this data that was at
least six months.
So it's not-e ven though sizedata and all the data is
(09:19):
available, it's still atime-consuming process to have
all the permissions in place andso on.
Patrick Sullivan (09:30):
Yeah, it's interesting because I think it's
a reminder that, even whenthese data systems exist and I
think we would all say it's agood thing that at each step
there's a question about what'sindividually identifiable,
what's not, what's coded, andunder what circumstances and
with what understanding were thedata collected and informs that
.
So thanks for reviewing thatfor us Again, like I'm
interested in the topic, butalso in just the potential of
(09:51):
these national data sources thatare linked, so thanks for
sharing a little bit more aboutthat with us.
So I want to wrap up this partby asking what you think the
implications of your findingsare for breast cancer prevention
.
What new recommendations wouldyou make?
Or sometimes our research justraises new questions that get us
on that path.
So what do you think theimplications are here?
Dorthe Pedersen (10:13):
I think, first of all, I would like to say,
because we find that a higherBMI in childhood is actually
seems to be protective againstbreast cancer risk.
I think it's important toemphasize that we do not
recommend girls to gain weightin order to prevent breast
cancer, because all in allobesity is associated with
multiple other adverse healthoutcomes and also several other
cancer forms.
So let us be clear that we arenot recommending this.
(10:36):
But in addition to this, Ithink our results are first step
.
So I think more studies aredefinitely needed before we can
start talking about how this canfeed into other preventive
initiatives, unfortunately.
But I definitely think that,because our results showed that
some of the associated wasmediated by breast density,
there also appears to be adirect effect of the BMI on the
(10:58):
breast cancer risk itself, whichis also supported by a
mendelian randomization studyconducted in the UK Biobank.
So I think it's reallyimportant to look into these
mechanisms before we can starttalking about preventive efforts
.
But yeah, perhaps it will makeus smarter in the future.
Patrick Sullivan (11:16):
I think that is the goal.
You know, like everything's onestep at a time, yeah, so I want
to turn now to a little bitabout some of the human side of
you know how we do our work, howwe come up with our questions
and our identities as people whodo research.
And maybe, starting just to askwhat motivated you to think
about this potentialrelationship between childhood
(11:37):
body size, pubertal timing,postmenopausal breast cancer?
And so, just from a scientificpoint of view, what informs that
?
But also, how did you choosebreast density as the potential
mediator?
So how do you put all thistogether before you started?
Dorthe Pedersen (11:53):
First of all, I'm lucky to be in a research
group where I can build onothers efforts.
So my primary supervisor, mymentor, had this research
project where we were lookinginto different associations with
childhood body size in relationto breast cancer.
So we also did other studies,but for this particular one we
were definitely motivated by theparadox- obesity paradox in
(12:15):
breast cancer.
That is, that we see that ahigh BMI in adulthood is
associated with a high risk ofbreast cancer, postmenopausal
breast cancer.
But when we look in childhoodwe see that a high BMI in
childhood appears to beprotective against
postmenopausal breast cancer andnormally we think that BMI
tracks from childhood toadulthood.
So this is truly a paradox.
(12:37):
We have also, before this,conducted another study where we
were able to generate BMItrajectories across the life
course in a smaller subsampleand from this we saw signals
that it's also the timing thatmatters for the breast cancer
risk.
So those who gain weight earlyon have a lower risk compared to
those who gain weight later inlife and those who gain weight
(12:58):
early in life don't get as highup as those who gain later in
life, if that makes sense.
But of course this is justsignals, but it motivated us to
look into what could thenexplain the association.
And the research group I wasworking with have previously
conducted a study in a differentsubset using a different
(13:20):
measure of breast density, wherethey also find some indication
of that.
It does play a role and becauseI think it's also biologically
possible that having excessweight around the time where the
breast develops that caninterfere with breast
development.
So that was also, it was alsobecause of the biology we
thought of this.
So yes that was how it was puttogether, and then the mediation
(13:44):
has not fully been examined inthe previous study.
So that really was what wewanted to do in this, also with
being able to try to quantifythe amount mediated, so yeah.
Patrick Sullivan (13:55):
Thank you.
So did anything that you foundin this study sort of point you
in a future direction or raisethe next question for you?
Dorthe Pedersen (14:07):
Yeah, for me personally I would say no, not
really the breast cancer.
I'm mostly an epidemiologistand so for me it's more- I would
like to conduct more mediationanalysis in other parts of my
research.
But I definitely think that Ihope that other researchers will
pick up on these results,especially those more into
(14:27):
mechanisms, and try todisentangle how it is that we
see these associations not onlywith the breast entity but also
the more direct effects.
I think that might be somethingwith the genetics, but yeah, I
don't think we have the fulloverview of how genetics works
yet, but.
Patrick Sullivan (14:43):
And thanks for sharing that and this kind of
behind the paper, just part ofthe discussion-
I think it is really interestingwhat you identify, which is
that there are some folks who,as epidemiologists, have a deep
interest in, develop, have ordevelop these deep interest in
methodology.
That is a source of passion,which is amazing.
(15:04):
And there are other folks whomay start with a topical
interest and say, like I'm goingto pick and choose my
collaborators or what I'm goingto learn about to serve my
interest in, like I'm aninfectious disease
epidemiologist, so that andthat's sort of what what drives
me, and I just think it's such apart of the richness of our
profession that there are peoplewho sort of get on both parts
(15:26):
of that path, you know, and thencan bring those skills to other
research questions.
So great to see this as likesomething that sparks an
interest and a passion and thatyou're going to carry forward.
I'm always interested in howpeople get to what they do and
you've said a little bit aboutthis.
But I wonder who, or maybe whatyou think has been the biggest
(15:47):
influence in your career thatsort of led you to what you do
now and to asking these kinds ofquestions.
What put you on this path?
Dorthe Pedersen (15:55):
Yeah, that's a tough question, I think, because
it would be very difficult forme to pinpoint one person or one
thing.
I think a lot of things haveinfluenced my career and also,
you know, choosing to become aresearcher, like my parents,
reading books, and also I'vebeen very fortunate to have
great mentors around me who havegot a dedicated time to guide
me.
But I think for my interest inwomen's health, that actually
(16:19):
traced back to once I wastraveling in Tanzania where I
met some local women and youknow I had a conversation with
them and in less than 10 minutesthey had really taught me about
what privilege is and howeasily you can be blinded by
this, because they had a verydifferent view of women's health
and women's rights than I camewith.
(16:40):
So I think that really put on aspark.
Patrick Sullivan (16:43):
Yeah, that was a spark for your research.
Yeah, so what do you think aresome misconceptions about doing
research or being a researcher?
Dorthe Pedersen (16:54):
That's a great question.
I think two things come to mymind, and one is that people
often think that you have to bebright or very talented to
become a researcher.
But in other sectors I think itrequires that you are curious
and very persistent and you havea willingness to learn from
those around you.
And the other thing is that Ioften hear so you're doing
(17:16):
research.
It's all about new things,testing new hypotheses, getting
new ideas, but actually doingresearch is a very iterative
process, I think, so you keeprepeating the same steps over
and over again to refine yourhypothesis and or approach right
.
So I think people will besurprised that we do a lot of
repetitive work actually inresearch.
Patrick Sullivan (17:38):
Yeah, I think this idea about developing
hypotheses is interestingbecause it speaks to the
different pieces of our sort ofprofessional identities that are
needed to do impactful scienceright, because you do need the
mathematical, the ability towork on that code until it runs,
to interpret the coefficients,to experimentiate things or like
(18:00):
whatever.
You know how are we getting tothe estimates?
But this idea of iterating ideasand our social scientific
networks, that are the soundingboards for us to say, you know,
to articulate ideas orarticulate questions, and what
an amazing professional resourceit is.
When you find yourself in aplace that you can put out a
(18:22):
question and I know for myself,like I always have, there's some
my mind runs a little bit andsays like I don't want to ask
this if somebody has alreadyanswered it and I'm not sure
I've thought through, like ifyou could even get that data,
and so it can be this kind ofself-censoring around our own
feelings of vulnerability orlike recognizing what we don't
know.
But that is the richness ofbeing in a research group, that
(18:45):
is a richness of being, you know, with colleagues, where you
develop that level of comfort,where you can really iterate
together and I think about howmany times like I've come up
with an idea that I thought wasgood and then threw it out, and
maybe then I decided it wasn'tso good, but by the time the
discussion was over, like weended up in a place that was far
better than what I would havecome up with, and so that sort
(19:07):
of scientific village, you know.
Dorthe Pedersen (19:10):
Yeah, I know that process.
It's a hard one but it'srewarding when you get to the,
when you actually get an ideayou think is much better than
the initial one.
Patrick Sullivan (19:20):
Yeah, and then you know related but maybe a
little bit different what advicewould you have for people who
are thinking about being aresearcher either, in terms of
how to prepare, how to decidethings you wish you'd thought
about early on?
Dorthe Pedersen (19:34):
Ah, I think my overall is just to go for it,
actually.
I think, although it's hardwork at times, it's also very
rewarding, as we just talkedabout, when you finally get that
idea that is perhaps new orperhaps helps you crack
something, a problem, orsomething that's fulfilling.
Patrick Sullivan (19:53):
Sometimes we call that the aha moment, like
after thinking and thinking andturning the gears, a little
moment of like aha, like that'sthere actually is a way to do
that.
Yeah, exactly, I find that Iget that more often like hanging
out with colleagues than inmoments of solitude.
But I think different people dodifferent ways.
I definitely know people whoretreat and come back out three
(20:15):
days later with everythingmapped out and I sort of work
well in a social scientificsetting where we brainstorm and
all different ways to do it forsure.
Dorthe Pedersen (20:25):
Yeah, but I think for me it's both.
I think I need some solitudesometimes to really process all
the information, and then, ofcourse, I need to test it with
someone else.
I think learning is somethingyou do in collaboration with
others.
I think it's difficult to do byyourself.
So, yeah, at some point it doesrequire some input.
But also for advice for perhapspeople wanting to pursue a
(20:48):
research career.
I also just want to say thatthey should remember that doing
research is a team effort, as wejust discussed, so they should
always act with this in mind, bekind to people and share credit
and stuff like this, and try tofind a supervisor or mentor
who's also on board with theresearch as a team effort and
(21:08):
not, yeah, just wanted to belonely genius.
Patrick Sullivan (21:14):
That sounds like an amazing place to wrap
this up.
Just the role role of beingkind, seeking mentorship, being
humble, takes us so much fartherthan other ways to get at these
problems.
So thank you, thank you for allthat you shared with us and for
that great sort of thought inwrapping up that brings us to
(21:35):
the end of this episode.
Thank you again, Dr.
Pedersen, for joining us today.
It's been such a pleasure tohave you on the podcast.
Dorthe Pedersen (21:42):
Thank you for inviting me on the podcast.
It was a pleasure toparticipate and I like the
discussion or the greatthoughtful questions.
Patrick Sullivan (21:52):
I'm your host, Patrick Sullivan.
Thanks for tuning in to thisepisode and see you next time on
EPITalk.
Brought to you by Annals ofEpidemiology, the official
journal of the American Collegeof Epidemiology.
For a transcript of thispodcast or to read the article
featured on this episode andmore from the journal, you can
visit us online at www.
(22:13):
annalsofepidemiology.
org.
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